Steering the course of CAR T cell therapy with lipid nanoparticles

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 28, 2024

Abstract Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, improved safety. Promising preclinical results signal a shift toward safer more effective CAR treatments. Ongoing research aims to validate these findings clinical trials, marking new era guided by LNPs utility therapy. Herein, we explore the preference for over methods, highlighting versatility of their delivery nucleic acids. Additionally, address key considerations, heralding Graphical

Язык: Английский

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In vivo vectorization and delivery systems for gene therapies and RNA-based therapeutics in oncology

Nanoscale, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Gene and RNA-based therapeutics represent a promising frontier in oncology, enabling targeted modulation of tumor-associated genes proteins. This review explores the latest advances payload vectorization delivery systems developed for vivo cancer treatments. We discuss viral non-viral organic particles, including lipid based nanoparticles polymeric structures, effective transport plasmids, siRNA, self-amplifying RNA therapeutics. Their physicochemical properties, strategies to overcome intracellular barriers, innovations cell-based carriers engineered extracellular vesicles are highlighted. Moreover, we consider oncolytic viruses, novel capsid modifications, approaches that refine tumor targeting immunomodulation. Ongoing clinical trials regulatory frameworks guide future directions emphasize need safe, scalable production. The potential convergence these with combination therapies paves way toward personalized medicine.

Язык: Английский

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Fluoroalkane modified cationic polymers for personalized mRNA cancer vaccines

Chemical Engineering Journal, Год журнала: 2022, Номер 456, С. 140930 - 140930

Опубликована: Дек. 12, 2022

Язык: Английский

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Biomimetic Mineralized CRISPR/Cas RNA Nanoparticles for Efficient Tumor-Specific Multiplex Gene Editing

ACS Nano, Год журнала: 2023, Номер 17(15), С. 15025 - 15043

Опубликована: Июль 23, 2023

CRISPR/Cas9 systems have great potential to achieve sophisticated gene therapy and cell engineering by editing multiple genomic loci. However, efficient multiplex editing, the delivery system needs adequate capacity transfect all RNA species at required stoichiometry into cytosol of each individual cell. Herein, inspired biomineralization in nature, we develop an all-in-one biomimetic mineralized system. This allows for precise control over coencapsulation ratio between Cas9 mRNA sgRNAs, while also exhibiting a high loading capacity. In addition, it enhances storage stability 4 °C up one month, surface nanoparticles can be easily functionalized targeting vivo nonliver sites. Based on above characteristics, as proof-of-concept, our was able significant gene-editing target (Survivin: 31.9%, PLK1: 24.41%, HPV: 23.2%) promote apoptosis HeLa cells mouse model, inhibiting tumor growth without obvious off-target effects liver tissue. addresses various challenges associated with multicomponent vivo, providing innovative strategy RNA-based editing.

Язык: Английский

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Cellular Trafficking of Nanotechnology‐Mediated mRNA Delivery

Advanced Materials, Год журнала: 2023, Номер 36(13)

Опубликована: Ноя. 6, 2023

Abstract Messenger RNA (mRNA)‐based therapy has emerged as a powerful, safe, and rapidly scalable therapeutic approach that involves technologies for both mRNA itself the delivery vehicle. Although there are some unique challenges different applications of therapy, common challenge all therapeutics is transport into target cell cytoplasm sufficient protein expression. This review focused on behaviors at cellular level nanotechnology‐mediated systems, which have not been comprehensively reviewed yet. First, four main introduced, including immunotherapy, replacement genome editing, reprogramming. Second, types cargos systems summarized. Third, strategies to enhance efficiency during trafficking process highlighted, accumulation cell, internalization endosomal escape, release from nanocarrier, translation protein. Finally, opportunities development presented. can provide new insights future fabrication nanocarriers with desirable performance.

Язык: Английский

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Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines

npj Vaccines, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 23, 2024

Abstract The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts improve vaccine formulation and efficacy. extraordinary advantages lipid nanoparticles (LNPs), including versatile design, scalability, reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating variants. Here, we assess the efficacy LNP-encapsulated booster encoding spike protein concern (Delta, Omicron) using a predecessor (YN2016C isolated from bats) strain elicit durable cross-protective neutralizing antibody responses. mRNA-LNP have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), high encapsulation efficiency (>90%). We employ in vivo bioluminescence imaging illustrate capacity our LNPs induce robust expression secondary lymphoid organs. In BALB/c mouse model, three-dose subcutaneous immunization mRNA-LNPs achieved remarkably levels cross-neutralization Omicron B1.1.529 BA.2 extended periods time (28 weeks) good safety profiles all constructs when used regime, YN2016C bat virus sequences. These findings important implications design aim trigger immunity current newly emerging

Язык: Английский

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Comprehensive analysis of lipid nanoparticle formulation and preparation for RNA delivery

International Journal of Pharmaceutics X, Год журнала: 2024, Номер 8, С. 100283 - 100283

Опубликована: Сен. 10, 2024

Язык: Английский

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Chimeric Antigen Cytotoxic Receptors for In Vivo Engineering of Tumor-Targeting NK Cells

ImmunoHorizons, Год журнала: 2024, Номер 8(1), С. 97 - 105

Опубликована: Янв. 1, 2024

Abstract Chimeric Ag receptor (CAR) NK cells are challenging to manufacture and fail achieve consistent tumor infiltration sustained cytolytic function in the microenvironment. In vivo engineering of using mRNA-based CAR delivery may overcome these issues. this study, we developed an programming method by designing CARs that leverage biology cell receptors for type–specific expression function. These were engineered fusion a recognition domain with natural cytotoxic family including NKp30, NKp44, NKp46. Our results demonstrated receptor–based can engage endogenous signaling adaptors effectively activate human lysis cytokine production. Specifically, discovered stable NKp44-based was contingent on presence immune cell–specific adaptor DAP12. This innovative strategy facilitates direct situ cells, enhancing safety minimizing off-target effects nontargeted, healthy tissues.

Язык: Английский

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Development of polypeptide-based materials toward messenger RNA delivery

Nanoscale, Год журнала: 2023, Номер 16(5), С. 2250 - 2264

Опубликована: Дек. 26, 2023

Messenger RNA (mRNA)-based therapeutic agents have demonstrated significant potential in recent times, particularly the context of COVID-19 pandemic outbreak. As a promising prophylactic and strategy, polypeptide-based mRNA delivery systems attract interest because their low cost, simple preparation, tuneable sizes morphology, convenient large-scale production, biocompatibility, biodegradability. In this review, we begin with brief discussion synthesis polypeptides, followed by review commonly used polypeptides delivery, including classical cell-penetrating peptides. Then, challenges against extracellular, intracellular, clinical barriers, are discussed detail. Finally, highlight range strategies for offering valuable insights into advancement carrier development.

Язык: Английский

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Artificial Breakthrough of Cell Membrane Barrier for Transmembrane Substance Exchange: A Review of Recent Progress

Advanced Functional Materials, Год журнала: 2023, Номер 34(13)

Опубликована: Дек. 15, 2023

Abstract Cell membrane composed of lipid bilayer is a selectively permeable that only allows specific molecules to pass through. While such selectivity essential for the survival and function cells, there exist instances when it necessary overcome cell barrier. Study on artificial barrier breakthrough strategies great significance development drug delivery systems understanding cellular behaviors. Herein, advancements in opening barriers over past decade are summarized. The main transmembrane mechanisms elucidated then divided into three categories, i.e., perforation via microinjection/external physical fields, endocytosis‐assisted construction channels, untethered micro/nanomachines. Next, potential applications after discussed, which mainly focus cargo endogenous substance extraction out from cell. Finally, this review outlines current challenges impede realization practical presents an outlook future opportunities promote further development. Through overcoming challenges, anticipated will provide revolutionized tool near advance field biomedicine biotechnology.

Язык: Английский

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